a study of selinexor (seli) + low-dose dexamethasone (ldd) in penta-refractory multiple myeloma (mm), seli and bortezomib + ldd in triple-class refractory mm.

Conditions: Multiple Myeloma, Refractory

Summary: the purpose of this study is to assess the efficacy, antitumor activity, safety and tolerability of selinexor plus low-dose dexamethasone in participants with penta-refractory multiple myeloma or selinexor and bortezomib plus low-dose dexamethasone in participants with triple-class refractory multiple myeloma.


Eligibility criteria:
inclusion criteria: * age greater than or equal to (\>=)18 years at the time of signing informed consent. * written informed consent in accordance with federal, local, and institutional guidelines. * measurable mm based on imwg guidelines as defined by at least one of the following: 1. serum m-protein \>= 0.5 gram per deciliter (g/dl) by serum protein electrophoresis (spep) or, for immunoglobulin (ig) a myeloma, by quantitative iga. 2. urinary m-protein excretion \>= 200 mg/24 hours. 3. free light chain (flc) \>= 100 milligram per liter (mg/l), provided that the flc ratio is abnormal. * only for arms sd-40 biw, sd-100 qw and sd-80 biw prior to protocol version (pv) 5.0: participants must have relapsed or refractory multiple myeloma (rrmm) and have previously received at least 4 anti-mm prior therapies and have mm that is refractory to previous treatment with at least 2 proteasome inhibitors (pis), at least 2 immunomodulatory agent (imids), and 1 anti-cluster of differentiation (cd38) monoclonal antibody. refractory is defined as lesser than or equal to (\<=) 25 percent (%) response to therapy, or progression during therapy or progression within 60 days after completion of therapy. * only for arms sd-40 biw and sd-100 qw as of pv 5.0: participants must have rr mm and have been previously treated with \>=3 anti-mm therapies (with exposure to at least 2 pi drugs, at least 2 imids, and 1 anti-cd38 monoclonal antibody), and be refractory to at least 1 drug of each class (pi/imid/anti-cd38). refractory is defined as \<=25% response to therapy or progression during therapy or progression within 60 days after completion of therapy. * only for arm svd: participants must have previously received 1 to 5 anti-mm prior therapies and have mm that is refractory to previous treatment with at least 1 pi, at least 1 imid, and 1 anti- cd38 monoclonal antibody. * eastern cooperative oncology group (ecog) performance status of \<= 2. * female participants of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. for both male and female participants, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment. exclusion criteria: * active plasma cell leukemia. * documented systemic amyloid light chain amyloidosis. * active central nervous system mm. * only for svd arm: greater than grade 2 peripheral neuropathy or grade \>= 2 peripheral neuropathy with pain at baseline, regardless of whether or not the participant is currently receiving medication. * radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) \<= 2 weeks prior to cycle 1 day 1 (c1d1). (steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to c1d1). * active graft vs. host disease (after allogeneic stem cell transplantation) at c1d1. * ongoing clinically significant non-hematological toxicities from prior treatments that are grade greater than (\>) 2 at c1d1. * inadequate hepatic function defined as total bilirubin \>= 2x upper limit of normal (uln) (\>= 3x uln for participants with gilbert's syndrome), aspartate transaminase (ast) \>= 2.5x uln, and alanine transaminase (alt) \>= 2.5x uln. * inadequate renal function defined as estimated creatinine clearance of lesser than (\<) 20 milliliter per minute (ml/min), calculated using the formula of cockroft and gault. * inadequate hematopoietic function defined as the following: 1. absolute neutrophil count (anc) \< 1000/cubic millimeter (mm\^3) 2. platelet count \< 75,000/mm\^3 3. hemoglobin (hb) level \< 8.5 g/dl * life expectancy of \< 4 months, based on the opinion of the investigator. * major surgery within 4 weeks prior to c1d1. * uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose. * active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment. * known active hepatitis a, b, or c infection; or known to be positive for hepatitis c virus rna or hepatitis b virus surface antigen. * female participants who are pregnant or lactating. * known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at c1d1. * concurrent therapy with approved or investigational anticancer therapeutic including topical therapies. * prior exposure to a sine compound, including selinexor. * serious, active psychiatric or active medical conditions which, in the opinion of the investigator or the sponsor, could interfere with the participation in the study. * contraindication to any of the required concomitant drugs or supportive treatments.

Keywords: multiple myeloma selinexor penta-refractory multiple myeloma triple-class refractory multiple myeloma kpt-330